thrombotic disorders Flashcards
what are thrombotic risk factors?
- post operative (especially orthopaedic)
- hospitalisation
- cancer
- pregnancy
- OCP
- long-haul flights
- obesity
- IV drug use
what presents when you have deep vein thrombosis?
- can be no symptoms at all
- unilateral calf swelling/heat/pain/redness/hardness
- differential diagnosis: cellulitis, Bakers’ cyst, muscular pain
- potentially fatal if missed
what is a doppler ultrasound?
transducer produces real-time two dimensional image of soft tissue structure
what shows velocity and direction of blood flow?
colour duplex
what is Doppler ultrasound used for?
- veins are non-compressible by U/S probe
- investigation of choice
- venogram done in past
what is the D-dimer test?
a test that assesses the likelihood of having a deep vein thrombosis
what do D-dimers do?
indicate activation of the clotting cascade
what do the results of a D-dimer show?
- low wells score and negative D-dimer test have a high negative predictive value
- high wells score or positive D-dimer then proceed to U/S scan to confirm DVT
what is the initial treatment of a deep vein thrombosis?
- therapeutic anti-coagulation using sub-cut LMW heparin (such as tinzaparin or enoxaparin)
- dose of LMW heparin according to patients weight
- no monitoring required (can use anti-Xa assay)
- ensure adequate EGFR >30ml/min
- otherwise use iv unfractionated heparin
what do you do when you have your first deep vein thrombosis?
anti-coagulated for 6 months
what do you do when you have your second deep vein thrombosis
lifelong anticoagulation
what is a PE?
pulmonary embolus
what are the symptoms of a PE?
- pleuritic pain
- dyspnoea
- haemoptysis
- syncope
- death
- tachycardia
- tachypnoea
- hypotension
what is a V/Q san?
ventilation/perfusion radio-isotope scan
what does under-perfusion lead to?
V/Q mismatch
what is the limitation of a V/Q scan?
underlying disease
what shows on an ECG when you have deep vein thrombosis?
- sinus tachycardia
- atrial fibrillation
- right heart strain (RBBB)
- classic: SI, QIII, TIII (rare)
what are the PE outcomes?
- 5% mortality rate despite treatment
- 4% develop pulmonary hypertension
- cause of death in 10-30% of in-patient post-mortems
- up to 60% have micro-emboli at post-mortem
- a leading cause of preventable death in the western world
how do you treat a massive PE?
- Mx: thrombolysis with tPA (alteplase), tissue plasminogen activator
- iv unfractionated heparin (monitor with APTR)
how do you treat a standard PE?
- LMW heparin injections
- warfarin for 6 months
- consider underlying causes
- LMW heparin is better if underlying cancer
- IVC filters
- consider a DOAC as an alternative (dabigatran po, rivaroxaban po)
what are inherited causes of thrombophilia screen?
- factor V leiden
- deficiency of natural anticoagulants (anti-thrombin deficiency, protein c deficiency, protein s deficiency)
what are the acquired causes of thrombophilia?
- anti-phospholipid syndrome
- test for lupus anticoagulant (DRVVT) and anticardiolipin Abs
what are examples of anti-thrombotics?
- warfarin
- heparin
- newer agens
- anti-platelets drugs
- fibrinolytic agents
what is warfarin?
a vitamin K antagonist that prevents gamma- carboxylation of factors II, VII, IX, X
what prolongs the extrinsic pathway?
warfarin
what monitors warfarin?
international normalised ratio
what is the international normalised ratio for warfarin?
2.5 for DVT, PE and AF and 3.5 for recurrent VTE or metal heart valves
what are the half-lives for the different clotting factor?
VII - 6 hours
IX - 24 hours
X - 40 hours
II - 60 hours
what natural anti-coagulants does warfarin inhibit?
- protein c
- protein s
what inhibits and induces warfarin?
- enzyme inhibitors potentiate warfarin
- enzyme inducers inhibit warfarin
how does alcohol interact with warfarin?
- binge drinking tends to potentiate warfarin
- chronic alcoholism tends to inhibit warfarin
what is warfarin control affected by?
- binding to albumin
- absorption of vitamin k from GI tract
- synthesis of vitamin k factor by liver
- hereditary resistance
what are the side-effects of warfarin?
- teratogenic
- significant haemorrhage risk
- minor bleeding up to 20% per year
- skin necrosis
- alopecia
how do you reverse warfarin?
in life-threatening bleeds you give activated prothrombin complex which contains vitamin k dependent factors II, VII, IX and X
what does do you give activated prothrombin in?
25-50 units per kg depending on INR level
what other treatments can you give to reverse warfarin?
- give vitamin K 2-10mg depending on INR level
- fresh frozen plasma (FFP) but it is not optimised for warfarin reversal
what is heparin?
mucopolysaccharide that works by potentiating anti-thrombin
what does heparin do?
irreversibly inactivates factor IIa and factor Xa
how is heparin administered?
by an injection
what are the 2 formulations of heparin?
- unfactionated heparin given by iv infusion
- low molecular weight heparin given sc injections
how is unfactionated heparin given?
iv with 5000U bolus and ~1000U/hour infusion
what is unfactionated heparin safe for?
renal failure as it is metabolised by the liver and not renally excreted
what is a rare complication or heparin?
heparin-induced thrombocytopenia
why is low molecular weight heparin convenient?
due to once daily sc injections and prescribed due to the patient’s weight
what must a patient have before being prescribed low molecular weight heparin?
creatine clearance of over 30ml/minute
what were direct oral anti-coagulants developed as?
oral alternatives to warfarin
what are benefits to direct oral anti-coagulants?
no monitoring required, flat dosing, good safety profile
what are the 2 classes of direct oral anti-coagulants?
- direct thrombin inhibitor
- direct factor Xa inhibitor
what is Rivaroxaban?
a direct factor Xa inhibitor which causes irreversible anti-coagulation
what are the signs that indicate you need to use Rivaroxaban?
- VTE prophylaxis
- used for treatment of DVTs and PEs
- stroke prevention in atrial fibrillation
what is an alternative to rivaroxaban?
apixaban
what is dabigatran?
a direct thrombin inhibitor
what are the signs that indicate you need to use dabigatran?
- VTE prophylaxis
- used for treatment of DVTs and PEs
- stroke prevention in arial fibrillation
what reverses dabigatran?
Praxbind
what are different types of anti-platelet drugs?
- aspirin (cyclo-oxygenase inhibitor)
- clopidogrel (ADP receptor blocker)
- dupyridamole (inhibits phosphodiesterase)
- prostacyclin (stimulates adenylate cyclase)
- glycoprotein IIb/IIIa inhibitors
what procedure are anti-platelet drugs used in?
angioplasty procedures
what are fibrinolytic agents?
thrombotic agents used to lyse fresh thrombi by converting plasminogen to plasmin
what are examples of fibrinolytic agents?
- tissue plasminogen activator (tPA, Alteplase)
- streptokinase
- urokinase
when are fibrinolytic agents administered?
systemically in actute MI, recent thrombotic stroke, major PE or massive iliofemoral thrombosis
what are the risks/things you need to be aware of with fibrinolytic agents?
- beware of contra-indicators to thrombolysis
- risk-benefit ratio = haemorrhage/thrombotic risk balance
